Kynurenine Aminotransferase Isozyme Inhibitors: A Review

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Kynurenine Aminotransferase Isozyme Inhibitors: A Review

Kynurenine aminotransferase isozymes (KATs 1-4) are members of the pyridoxal-5'-phosphate (PLP)-dependent enzyme family, which catalyse the permanent conversion of l-kynurenine (l-KYN) to kynurenic acid (KYNA), a known neuroactive agent. As KATs are found in the mammalian brain and have key roles in the kynurenine pathway, involved in different categories of central nervous system (CNS) disease...

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Intramitochondrial localization of kynurenine aminotransferase.

Comparisons with the distribution of intramitochondrial marker enzymes have indicated that kynurenine aminotransferase is present in the inner membrane fraction of rat liver mitochondria. It appears to be weakly bound to the inner membrane because it is easily solubilized by increasing the concentration of digitonin. With the use of a-ketoglutarate or oxalacetate as amino group acceptor, the am...

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Crystal structure of human kynurenine aminotransferase I.

The kynurenine pathway has long been regarded as a valuable target for the treatment of several neurological disorders accompanied by unbalanced levels of metabolites along the catabolic cascade, kynurenic acid among them. The irreversible transamination of kynurenine is the sole source of kynurenic acid, and it is catalyzed by different isoforms of the 5'-pyridoxal phosphate-dependent kynureni...

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Biochemical and phenotypic abnormalities in kynurenine aminotransferase II-deficient mice.

Kynurenic acid (KYNA) can act as an endogenous modulator of excitatory neurotransmission and has been implicated in the pathogenesis of several neurological and psychiatric diseases. To evaluate its role in the brain, we disrupted the murine gene for kynurenine aminotransferase II (KAT II), the principal enzyme responsible for the synthesis of KYNA in the rat brain. mKat-2(-/-) mice showed no d...

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Characteristic Features of Kynurenine Aminotransferase Allosterically Regulated by (Alpha)-Ketoglutarate in Cooperation with Kynurenine

Kynurenine aminotransferase from Pyrococcus horikoshii OT3 (PhKAT), which is a homodimeric protein, catalyzes the conversion of kynurenine (KYN) to kynurenic acid (KYNA). We analyzed the transaminase reaction mechanisms of this protein with pyridoxal-5'-phosphate (PLP), KYN and α-ketoglutaric acid (2OG) or oxaloacetic acid (OXA). 2OG significantly inhibited KAT activities in kinetic analyses, s...

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ژورنال

عنوان ژورنال: International Journal of Molecular Sciences

سال: 2016

ISSN: 1422-0067

DOI: 10.3390/ijms17060946